title: Recruitment of the autophagic machinery to endosomes during infection is mediated by ubiquitin.
abstract: Although ubiquitin is thought to be important for the autophagic sequestration of invading bacteria (also called xenophagy), its precise role remains largely enigmatic. Here we determined how ubiquitin is involved in this process. After invasion, ubiquitin is conjugated to host cellular proteins in endosomes that contain Salmonella or transfection reagent-coated latex (polystyrene) beads, which mimic invading bacteria. Ubiquitin is recognized by the autophagic machinery independently of the LC3-ubiquitin interaction through adaptor proteins, including a direct interaction between ubiquitin and Atg16L1. To ensure that invading pathogens are captured and degraded, Atg16L1 targeting is secured by two backup systems that anchor Atg16L1 to ubiquitin-decorated endosomes. Thus, we reveal that ubiquitin is a pivotal molecule that connects bacteria-containing endosomes with the autophagic machinery upstream of LC3.
authors.affiliation: Department of Genetics, Graduate School of Medicine, 2 Laboratory of Intracellular Membrane Dynamics, Graduate school of Frontier Biosciences, 3 Department of Molecular Virology, Research Institute for Microbial Diseases, 4 Department of Host Defense, WPI Immunology Frontier Research Center, 5 Department of Host Defense, Research Institute for Microbial Disease, and 6 Core Instrumentation Facility, Research Institute for Microbial Disease, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Naonobu
authors.initials: N
authors.lastname: Fujita
authors.forename: Eiji
authors.initials: E
authors.lastname: Morita
authors.forename: Takashi
authors.initials: T
authors.lastname: Itoh
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanaka
authors.forename: Megumi
authors.initials: M
authors.lastname: Nakaoka
authors.forename: Yuki
authors.initials: Y
authors.lastname: Osada
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Umemoto
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Saitoh
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakatogawa
authors.forename: Shouhei
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Tokuko
authors.initials: T
authors.lastname: Haraguchi
authors.forename: Jun-Lin
authors.initials: JL
authors.lastname: Guan
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Iwai
authors.forename: Fuminori
authors.initials: F
authors.lastname: Tokunaga
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Saito
authors.forename: Koutaro
authors.initials: K
authors.lastname: Ishibashi
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Fukuda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Noda
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Yoshimori
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism* / Q000382:microbiology*; D057809:HEK293 Cells; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D041681:NIH 3T3 Cells; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C518959:ATG16L1 protein, human; C532820:Atg16l1 protein, mouse; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C477012:MAP1LC3A protein, human; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; C407704:RB1CC1 protein, human; C428743:Rb1cc1 protein, mouse; D025801:Ubiquitin; D011505:Protein-Tyrosine Kinases